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Omics

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Omics
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In this context, health care biomarkers are of major interest to deduce a person’s (or animal’s) health status in regard to specific markers such as Vitamin D, which directly affects bone mineralization and calcium regulation in the body [1].

The approach of general medical care is changing from broad-spectrum drugs towards personalized healthcare. The new trend is fueled by an increasing level of information flow, transparency, customization and patient choice, all together leading to new services. Patients are able to gather an enormous amount of medical data from the internet or even order blood and biomarker tests themselves. Direct analytical blood tests are already available for certain markers [2]. The growing awareness of healthcare issues and recent developments of minimally invasive blood biomarker tests show the huge future potential of this life science branch. In the future, personalized drug dosage could be established by almost online monitoring the particular biomarker, thus providing more safety for the patient based on smart dosages and dynamically updated dosage profiles [3]. Biomarker analysis is not only for monitoring a drug dosage, it can be applied much earlier – before the disease even appears.

[1] G. Nys, M. G. M. Kok, A. C. Servais, and M. Fillet, “Beyond dried blood spot: Current microsampling techniques in the context of biomedical applications,” TrAC – Trends Anal. Chem., vol. 97, pp. 326–332, 2017.

[2] T. Holen, F. Norheim, T. E. Gundersen, P. Mitry, J. Linseisen, P. O. Iversen, and C. A. Drevon, “Biomarkers for nutrient intake with focus on alternative sampling techniques,” Genes Nutr., vol. 11, no. 1, pp. 1–20, 2016.

[3] Y. Sandlers, “The future perspective: metabolomics in laboratory,” Transl. Res., pp. 1–11, 2017.

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Newborn Screening

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Newborn Screening
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Nowadays, a routine neonatal screening procedure requires that a health professional takes a few drops of blood from the baby’s heel, applies them onto filter paper and sends such prepared samples to a laboratory for a number of analytical tests. Current sample preparation taking place before analysis may be labor-intensive, time-consuming and not very precise due to carry-over when processed with traditional “punch-and-elute” methodology. Most laboratories still perform the MS analysis from one DBS disc and the biological assays from a second disc. Application of DBS-MS 500 will standardize the sample preparation process, while also simplifying the workflow and eliminating any manual working steps.

[1] B. L. Therrell, C. D. Padilla, J. G. Loeber, I. Kneisser, A. Saadallah, G. J. C. Borrajo, and J. Adams, “Current status of newborn screening worldwide: 2015,” Semin. Perinatol., vol. 39, no. 3, pp. 171–187, 2015.

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Therapeutic Drug Monitoring

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Therapeutic Drug Monitoring
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Doping Control

There has been a great dynamic around TDM related to DBS for the last 5 years. Personalized health care is a big topic in the pharma industry and DBS is a well-suited technique to monitor a patient’s drug uptake (ADME studies). Drugs that are required to be taken long term are especially appropriate. Enabling an “at home” sampling for patients would bring significant cost reductions and comfort for the patients [1]. The implementation of DBS-analysis avoids the requirement that patients need to visit the hospital several times to draw up to 5 mL of blood for plasma testing. With DBS, patients can draw samples by themselves at home and send them via standard mail to a centralized laboratory. Also, the correct administration of drugs can be monitored very easily by DBS [2]. Therefore, there is a clear trend of using DBS for monitoring anti-cancer drugs, antiretroviral drugs, antiepileptic drugs, immunosuppressive drugs, etc.

Illicit Drug Control

Urine is the preferred biological fluid to analyze the most commonly used performance-enhancing compounds. The collection of this biological fluid is non-invasive and cheap. However, blood testing is becoming more and more popular within the anti-doping and sports organizations, and thus the detection of forbidden substances or their metabolites in blood was included in the World Anti-Doping Agency (WADA) prohibited list [1]. Blood analysis was not convenient for large-scale screening in the past, but with new DMS methods, it will replace the urine analysis to some extent, since for certain compounds it is more accurate and non-metabolized drugs can be found. Blood analysis provides a snapshot of the compounds in the bloodstream at the moment of sampling, whereas urine reflects the degradants of the compounds used over several days. There is a tendency that more and more DMS methods will be implemented within the next years, DMS will certainly gain popularity in this market.

[1] A. J. Wilhelm, J. C. G. den Burger, and E. L. Swart, “Therapeutic Drug Monitoring by Dried Blood Spot: Progress to Date and Future Directions,” Clin. Pharmacokinet., vol. 53, no. 11, pp. 961–973, 2014.

[2] M. H. U. Duthaler, B. Berger, S. Erb, M. Battegay, E. Letang, S. Gaugler, S. Krähenbühl, “Automated high throughput analysis of antiretroviral drugs in dried blood spots.,” J Mass Spectrom., vol. 52, no. 8, pp. 534–542, 2017.

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Clinical and Pre-Clinical Application

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Clinical and Pre-Clinical Application
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The pre-clinical and clinical market summarizes the testing of new pharmaceuticals in animal (pre-clinical) and human (clinical) studies. The main advantage in pre-clinical studies is the reduced number of test animals (due to the need for lower blood volumes) which is in accordance with the 3R requirement of animal studies (replacement, reduction, refinement) [1]. Drugs can be studied on a single mouse over several time points, whereas several mice are required with conventional methods. In clinical studies, there is an ease in sampling and more patient comfort.

The pre-clinical and clinical market summarizes the testing of new pharmaceuticals in animal (pre-clinical) and human (clinical) studies. The main advantage in pre-clinical studies is the reduced number of test animals (due to the need for lower blood volumes) which is in accordance with the 3R requirement of animal studies (replacement, reduction, refinement) [1]. Drugs can be studied on a single mouse over several time points, whereas several mice are required with conventional methods. In clinical studies, there is an ease in sampling and more patient comfort.

The DBS technology offers huge advantages here, however has not been fully accepted by regulatory bodies so far [2]. The major reason for this is the hematocrit effect based on different blood viscosity. If a sub-punch is taken and the hematocrit value and the volume is unknown, an analytical error may result. However, this only results in a significant error if the hematocrit value is outside of the normal range (40 to 54% for men and 36 to 48% for women [3]) of a healthy patient. Also, in most clinical studies the patient hematocrit value is known.

[1] R. V Oliveira, J. Henion, and E. R. Wickremsinhe, “Automated high-capacity on-line extraction and bioanalysis of dried blood spot samples using liquid chromatography/high-resolution accurate mass spectrometry.,” Rapid Commun. Mass Spectrom., vol. 28, no. 22, pp. 2415–26, Nov. 2014.

[2] N. Ganz, M. Singrasa, L. Nicolas, M. Gutierrez, J. Dingemanse, W. Döbelin, and M. Glinski, “Development and validation of a fully automated online human dried blood spot analysis of bosentan and its metabolites using the Sample Card And Prep DBS System.,” J. Chromatogr. B. Analyt. Technol. Biomed. Life Sci., vol. 885–886, pp. 50–60, Feb. 2012.

[3] H. Walker, W. Hall, and J. Hurst, Clinical Methods: The History, Physical, and Laboratory Examinations, 3rd editio. 1990.

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Other (DBS)

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Other
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DBS is part of a wider term defined as dried matrix spot (DMS). Basically, the filter paper card can act as a carrier for any matrix enabling fully automated extraction and analysis from a dried probe. CAMAG currently focuses on LC-MS applications, however a huge variety of different methods, such as genetic procedures, biological assays or ICP-MS applications, have been published and may be accessible as well. The possibilities in this field are vast. New and creative analytical workflows can be established. One example is the automated analysis concept of Gutter oil from filter paper cards. Gutter oil describes illicit cooking oil which has been recycled from discarded used oil. The filter paper is a perfect sample collector and sample carrier to monitor the quality of cooking oil in restaurants.

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